1: Mol Cell Biol. 1998 Jun;18(6):3310-20. 

TFII-I enhances activation of the c-fos promoter through interactions with
upstream elements.

Kim DW, Cheriyath V, Roy AL, Cochran BH.

Department of Cellular and Molecular Physiology, Tufts University School of
Medicine, Boston, Massachusetts 02111, USA.

The transcription factor TFII-I was initially isolated as a factor that can bind
to initiator elements in core promoters. Recent evidence suggests that TFII-I
may also have a role in signal transduction. We have found that overexpression
of TFII-I can enhance the response of the wild-type c-fos promoter to a variety
of stimuli. This effect depends on the c-fos c-sis-platelet-derived growth
factor-inducible factor binding element (SIE) and serum response element (SRE).
There is no effect of cotransfected TFII-I on the TATA box containing the c-fos
basal promoter. Three TFII-I binding sites can be found in c-fos promoter. Two
of these overlap the c-fos SIE and SRE, and another is located just upstream of
the TATA box. Mutations that distinguish between serum response factor (SRF),
STAT, and TFII-I binding to the c-fos SIE and SRE suggest that the binding of
TFII-I to these elements is important for c-fos induction in conjunction with
the SRF and STAT transcription factors. Moreover, TFII-I can form in vivo
protein-protein complexes with the c-fos upstream activators SRF, STAT1, and
STAT3. These results suggest that TFII-I may mediate the functional
interdependence of the c-fos SIE and SRE elements. In addition, the ras pathway
is required for TFII-I to exert its effects on the c-fos promoter, and growth
factor stimulation enhances tyrosine phosphorylation of TFII-I. These results
indicate that TFII-I is involved in signal transduction as well as
transcriptional activation of the c-fos promoter.

PMID: 9584171 [PubMed - indexed for MEDLINE]


---------------------------------------------------------------


2: Blood. 1996 Oct 15;88(8):2906-16. 

Contribution of both STAT and SRF/TCF to c-fos promoter activation by
granulocyte-macrophage colony-stimulating factor.

Rajotte D, Sadowski HB, Haman A, Gopalbhai K, Meloche S, Liu L, Krystal G, Hoang
T.

Clinical Research Institute of Montreal, Quebec, Canada.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic
growth factor that has been shown to support call proliferation in murine
fibroblasts engineered to stably express both chains of the human GM-CSF
receptor (NIH-GMR). Because the proto-oncogene c-fos is believed to provide a
link between short-term signals elicited at the membrane and long-term cellular
response, we chose to study the mechanism of GM-CSF-dependent cell regulation
using c-fos promoter activity as a molecular marker in both NIH-GMR
transfectants and in the CD34+ cell line TF-1. The importance of c-fos and
related AP-1 activity in GM-CSF signalling was suggested by a tight correlation
between GM-CSF-dependent activation of the c-fos promoter and cell proliferation
and by the inhibitory effect of a trans-dominant c-fos mutant on cell growth. To
evaluate the contribution of the serum response factor (SRF) associated with the
ternary complex factor (TCF) and of STAT proteins to c-fos promoter activation
in response to GM-CSF, the SRF binding site (SRE) and/or the STAT binding site
(SIE) were inactivated. In serum-free medium, both SRE and SIE are essential to
c-fos promoter activation by GM-CSF in NIH-GMR transfectants and in TF-1 cells.
No response to GM-CSF was observed when both sites were mutated. The nature of
the STAT family member was further investigated by Wester blots and DNA
retardation assays using an SIE probe. Our data indicate that GM-CSF induced DNA
binding of both STAT1 and STAT3 in NIH-GMR and mainly of STAT3 in TF-1 cells.
STAT5 tyrosine phosphorylation was also observed in TF-1 cells. Finally,
expression of a dominant negative MAPK mutant, ERK192A, resulted in a decrease
of both SRE- and SIE-dependent activation of c-fos promoter by GM-CSF,
suggesting that STAT1/3 are regulated not only by tyrosine kinases, but also
partially by MAPK.

PMID: 8874187 [PubMed - indexed for MEDLINE]


---------------------------------------------------------------